The catalytic activity for the oxidation of isobutane catalyzed by 12-molybdophosphoric acid was much changed by the V5+- and Cs+-substitution for Mo6+ and H+, respectively. The best yield of methacrylic acid was 9.0% and was obtained for the heteropoly catalyst with V and Ca contents of 1 and 2.5, respectively. The high catalytic activity obtained for Cs2.5Ni0.08H1.34PVMo11O40 is presumably due to the high surface area. The activities of 12-molybdovanadophosphoric acids as well as those of 12-molybdophosphoric acid partially salified with Csf were controlled by the oxidizing ability of catalysts. The conversion vs selectivity relationships, the simulation of the data, and kinetic results for Cs2.5Ni0.08H1.34PVMo11O40 and Cs2.5Ni0.08H0.34PMo12O40 catalysts show that the first steps, i.e., selective and complete oxidation reactions of isobutane, are rate-determining and mainly catalyzed by molybdenum ion and that vanadium ion efficiently accelerates the selective oxidation of methacrolein to methacrylic acid. Cs+-substitution for H+ in H3.84Ni0.08PVMo11O40 greatly change the selectivity up to a Cs content of 2.5 and suppressed the elimination of the vanadium ion from the Keggin anion.